Dornhof Johannes, Kieninger Jochen, Rupitsch Stefan J, Weltin Andreas
Laboratory for Electrical Instrumentation and Embedded Systems, IMTEK - Department of Microsystems Engineering, University of Freiburg, Georges-Köhler-Allee 103, 79110 Freiburg, Germany.
Lab Chip. 2025 Feb 25;25(5):1149-1168. doi: 10.1039/d4lc00437j.
Cell cultures, organs-on-chip and microphysiological systems become increasingly relevant as models, , in drug development, disease modelling, toxicology or cancer research. It has been underlined repeatedly that culture conditions and metabolic cues have a strong or even essential influence on the reproducibility and validity of such experiments but are often not appropriately measured or controlled. Here we review microsensor systems for cell metabolism for the continuous measurement of culture conditions in microfluidic and lab-on-chip platforms. We identify building blocks, features and essential advantages to underline the relevance of these systems and to derive appropriate requirements for development and practical use. We discuss different formats and geometries of cell culture, microfluidics and the resulting consequences for sensor placement, as the prerequisite for understanding the various approaches and classification of the systems. The major chemical and biosensors based on electrochemical and optical principles are discussed for general understanding and to contextualize current developments. We then review selected recent sensor systems with real-world implementations of sensing in cell cultures and organs-on-chip, employing a helpful characterization. That includes formats and cell models, microfluidic systems and sensor types applied in static and dynamic monitoring of 2D and 3D cell cultures, as well as single spheroids. We discuss notable advances, particularly with respect to sensor performance and the demonstration of long-term continuous measurements. We outline current approaches to system fabrication technologies, material choice, and interfacing, and comment on recent trends. Finally, we conclude with critical remarks on the current state of sensors in cell culture monitoring and identify avenues for future improvements for both developers and users of such systems, which will lead to better and more predictive models.
细胞培养、芯片器官和微生理系统作为药物开发、疾病建模、毒理学或癌症研究中的模型，正变得越来越重要。人们反复强调，培养条件和代谢线索对这类实验的可重复性和有效性有很强甚至至关重要的影响，但往往没有得到适当的测量或控制。在此，我们综述用于细胞代谢的微传感器系统，以连续测量微流控和芯片实验室平台中的培养条件。我们确定构建模块、特征和基本优势，以强调这些系统的相关性，并得出对开发和实际应用的适当要求。我们讨论细胞培养、微流控的不同形式和几何形状以及对传感器放置的影响，这是理解系统的各种方法和分类的前提。基于电化学和光学原理的主要化学和生物传感器被讨论，以促进总体理解并将当前的发展情况置于背景之中。然后，我们综述了近期选定的传感器系统，这些系统在细胞培养和芯片器官中有实际的传感应用，并进行了有益的表征。这包括应用于二维和三维细胞培养以及单个球体的静态和动态监测的形式、细胞模型、微流控系统和传感器类型。我们讨论了显著的进展，特别是在传感器性能和长期连续测量的演示方面。我们概述了系统制造技术、材料选择和接口的当前方法，并对近期趋势进行了评论。最后，我们对细胞培养监测中传感器的当前状态提出批判性意见，并为这类系统的开发者和用户确定未来改进的途径，这将产生更好、更具预测性的模型。
